The isolated hepatocyte preparation provides a useful model system for investigation of hepatic lipid and lipoprotein synthesis. The simplified, enzyme-perfusion method that I devised will be used to prepare liver cells for biochemical studies. Ultrastructurally intact cells are isolated in high yield, and simulate the perfused liver in the their metabolic behavior. These hepatocytes rapidly incorporate precursors into lipids, proteins, and lipoproteins, respond to the in vitro addition of hormones and cyclic nucleotides, and can be maintained in suspension culture. The availability of many identical cell aliquots from the same liver diminishes the problem of inter-animal variation and simplifies the interpretation of data obtained. The proposed research is designed to gain information on the action of cyclic AMP and its derivatives on hepatic lipid, plasma lipoprotein synthesis and metabolism. Other objectives include elucidation of possible derangements in the regulation of lipogenesis by cyclic AMP and examination of the relationship between rates of production of lipids and plasma lipoproteins. Studies will be done with freshly prepared and with cultured hepatocytes to gain information on immediate and inductive effects. Both mammalian (rat, monkey) and avian (pigeon) hepatocytes will be employed in order to utilize the methodological advantages peculiar to each and potentially to broaden the scope of the information obtained. The degradation of I125-labeled rat and avian lower density lipoproteins by isolated hepatocytes prepared from the corresponding species has been and will continue to be examined.